Microglial reactivity predicts hippocampal, but not global, atrophy in cerebral small vessel disease
Adriana Zainurin1, Robin B Brown1, Daniel J Tozer1
1Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Introduction:
Cerebral small vessel disease (CSVD) is the most prevalent pathology underlying vascular dementia. Increased neuroinflammation and blood-brain barrier (BBB) permeability have been implicated in CSVD pathogenesis. We determined whether microglial reactivity and BBB permeability at baseline predicted whole-brain and hippocampal atrophy over one year, and cognitive impairment over four years.
Methods:
Seventy-seven patients with CSVD were recruited to this prospective study. Baseline microglial reactivity and BBB permeability were determined using 11C-PK11195 positron emission tomography and dynamic contrast enhanced (DCE) MRI respectively.
Results:
Greater 11C-PK11195 binding at baseline was associated with hippocampal atrophy over one year (p = 0.001), but not with global brain atrophy. Cox regression analyses showed no significant associations between 11C-PK11195 and cognitive impairment. There were no associations between BBB permeability with whole-brain and hippocampal atrophy, or with cognitive impairment.
Discussion:
Our data suggests that microglial reactivity may play a role in hippocampal atrophy; potentially contributing to the increasingly recognized interaction between vascular and neurodegenerative pathology.
Insights
Microglial reactivity, not blood-brain barrier permeability, predicted hippocampal atrophy in cerebral small vessel disease (CSVD) patients. This finding highlights neuroinflammation
Area of Science:
- Neuroimaging
- Neurology
- Vascular Dementia Research
Background:
- Cerebral small vessel disease (CSVD) is a primary cause of vascular dementia.
- Neuroinflammation and blood-brain barrier (BBB) permeability are implicated in CSVD.
- The relationship between baseline markers and long-term outcomes in CSVD requires further investigation.
Purpose of the Study:
- To determine if microglial reactivity and BBB permeability predict brain atrophy and cognitive decline in CSVD patients.
- To investigate the role of neuroinflammation in the progression of CSVD.
Main Methods:
- Seventy-seven CSVD patients underwent baseline 11C-PK11195 positron emission tomography and dynamic contrast-enhanced MRI.
- Microglial reactivity and BBB permeability were assessed using these imaging techniques.
- Brain atrophy and cognitive function were monitored over one and four years, respectively.
Main Results:
- Higher baseline 11C-PK11195 binding (microglial reactivity) correlated with hippocampal atrophy over one year (p=0.001).
- No significant association was found between microglial reactivity and global brain atrophy or cognitive impairment.
- Blood-brain barrier permeability did not predict atrophy or cognitive impairment.
Conclusions:
- Microglial reactivity may contribute to hippocampal atrophy in CSVD.
- These findings suggest an interaction between vascular pathology and neurodegeneration in CSVD.
- Further research is needed to explore the therapeutic potential of targeting neuroinflammation in CSVD.
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